Beyond hyponatremia: sodium-to-chloride ratio as a predictor of 1-year mortality in heart failure

Background

Hyponatremia is a well-established marker of adverse outcomes in heart failure; however, emerging evidence indicates that hypochloremia is independently associated with increased mortality. The sodium-to-chloride (Na/Cl) ratio integrates information from both electrolytes and may better reflect electrolyte and acid–base disturbances, yet its prognostic value in heart failure remains unclear. This study aimed to evaluate the association between the Na/Cl ratio and 1-year mortality in patients with heart failure.

Methods

This observational study included 200 consecutive patients hospitalized with HF. Serum sodium and chloride levels were obtained during index hospitalization, and the Na/Cl ratio was calculated by dividing serum sodium by serum chloride levels. Logistic regression analyses and ROC analysis were performed to evaluate the association between the Na/Cl ratio and 1-year mortality.

Results

The study included 200 patients with heart failure, of whom 105 were men (52.5%). Heart failure etiology was ischemic in 95 patients (46.5%). Common comorbidities included hypertension in 159 patients (79.5%), diabetes mellitus in 83 patients (41.5%), atrial fibrillation in 98 patients (49.0%), and chronic kidney disease in 104 patients (52.0%). In-hospital mortality occurred in 8 patients (4.0%). During the 1-year follow-up period, 84 patients (42.0%) died.

Median serum sodium and chloride levels were 137 mmol/L (IQR 134–140) and 103 mmol/L (IQR 100–107), respectively, resulting in a median sodium-to-chloride (Na/Cl) ratio of 1.33 (IQR 1.29–1.37). Receiver operating characteristic (ROC) analysis demonstrated that the Na/Cl ratio had modest but statistically significant discriminatory ability for predicting 1-year mortality (AUC 0.618, 95% CI 0.539–0.697; p=0.004). A Na/Cl ratio cut-off value of 1.31 yielded a sensitivity of 72.6% and a specificity of 50.0% for predicting 1-year mortality.

In univariable logistic regression analysis, a Na/Cl ratio ≥1.31 was associated with increased 1-year mortality (OR 1.94, 95% CI 1.06–3.55; p=0.032). In the multivariable logistic regression model, an elevated Na/Cl ratio remained independently associated with 1-year mortality after adjustment for relevant clinical covariates (OR 2.85, 95% CI 1.42–5.70; p=0.003; Table 2). Advanced chronic kidney disease stage was also independently associated with increased mortality risk (OR 1.55, p=0.036), whereas higher hemoglobin levels were inversely associated with 1-year mortality (OR 0.78, p=0.002).

Conclusion

In patients hospitalized with heart failure, an elevated sodium-to-chloride ratio is independently associated with increased 1-year all-cause mortality. Although its discriminatory capacity is modest, the Na/Cl ratio provides incremental prognostic information beyond established clinical risk factors. Given its simplicity and routine availability, the Na/Cl ratio may serve as a complementary biomarker for risk stratification in patients with heart failure.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.